At present, cancer is the leading causal disease of death and a basic treatment method thereof has been demanded. For this end, many anti-cancer agents such as bleomycin, cisplatin, neocarzinostatin and the like have been developed. However, these anti-cancer agents could not provide a sufficient anti-cancer effect, since they have high toxicity and are less oriented to cancer. Therefore, various attempts have been made to make these anti-cancer agents more oriented to cancer, and one of such attempts is the development of a liposome preparation for administration of an anti-cancer agent enclosed inside the liposome. Liposome preparation is a preparation including a drug inside a particle having a bilayer membrane structure formed of phospholipid, and detailed analyses as regards cancer cell targeting have been performed.
Phospholipid is a major lipid constituting the biological membrane system, and is divided into glycerophospholipid having a glycerol skeleton, and sphingophospholipid having a sphingosine skeleton. Furthermore, depending on the kind of the hydrophilic moiety, glycerophospholipids are divided into phospholipid classes of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, cardiolipin, phosphatidic acid and the like.
As the functions of phospholipids, there have been reported, besides the role of a membrane-constituting component that divides cells and cell organelles, that inositol phospholipid has a known role as an intercellular signaling pathway by phospholipase C and an anchor of protein-membrane; phosphatidylserine regulates the activities of blood coagulation protein, protein kinase C and the like; sphingomyelin pathway is involved in the regulation of activity of protein kinase C and cell apoptosis; phosphatidylcholine pathway relates to the maintenance of arachidonic acid which is an inflammatory mediator and signal transduction pathway by phospholipase D; platelet-activating factor which is alkyl ether phospholipid shows platelet activation, blood vessel permeability, leukocyte migration activity; and the like, and the functions provided by the classes thereof vary widely.
For example, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine have been reported to improve spatial learning disorder and memory disorder induced by scopolamine, or mild cognitive impairment and dementia (non-patent documents 1, 2).
Also, phosphatidylethanolamine is a phospholipid, which is one of the main components of biological membrane, and is being marketed along with phosphatidylserine and the like as health foods. Of phosphatidylethanolamines, particularly, dilinoleoyl phosphatidylethanolamine (containing two linoleic acids as fatty acids) has been reported to have cell death inducing suppressive activity, particularly, endoplasmic reticulum stress suppressive activity and, due to such activity, dilinoleoyl phosphatidylethanolamine can be used for pharmaceutical application, particularly for the prophylaxis and/or treatment of neurodegenerative disease (patent document 1).